孕期血胆固醇水平异常升高（GHC）危害胎儿发育和子代健康，但机制不清，课题组前期研究表明HDL-C水平异常升高和胎盘功能紊乱可能是主要原因。本研究拟在已建立队列基础上扩大样本量，采用核磁共振仪分析孕妇血清HDL颗粒及其亚类的含量；密度梯度超离心分离HDL颗粒并检测其脂质组、蛋白组构成和抗氧化功能、气质联用色谱检测氧化固醇水平，研究GHC孕妇HDL颗粒的分布和功能变化及其与新生儿体重的关系及胎儿生长受限（FGR）发生的风险；分别用GHC和FGR孕妇的HDL颗粒和氧化固醇处理斑马鱼胚胎及人滋养层细胞，观察斑马鱼的存活率、畸形率、血管生成等，检测氧化应激、细胞生长和分化、IGF1R-PI3K/AKT信号通路等指标，同时检测GHC和FGR孕妇胎盘组织中上述指标及胎盘形态、血管密度等，确定HDL颗粒及氧化固醇对胎盘血管生成、胚胎发育和细胞分化的影响，揭示孕期血胆固醇水平异常升高抑制胎儿发育的机制。

Other researchers and our team have studied that gestational hypercholesterolemia impaired the placental function and might be related to the fetal growth restriction，but the mechanisms are unclear. The present study hypothesized that the HDL subclasses and compositions were changed in hypercholesterolemic pregnant women and then the antioxidantive and antiinflammative function of HDL particals were impaired. So, pregnant women in early gestation were recruited and the birth cohort was established to confirm the risk of genstational hypercholesterolemia on fetal growth. And then HDL partical was separated from pregnant women by polyacrylamide gel electrophoresis, lipidomic and proteomic analyzing the composition, and the antioxidative ability were also measured in vitro. The HDL subclasses and distribution in normal and hypercholesterolemic pregnancy were studied by MRI. The relationship of HDL particals levels and birthweight were analyzed by multivariable linear regression and the OR value for fetal growth restriction was calculated by logistic regression. .The zebrafish were fed with control or high cholesterol diet, and the embyo were injected with HDL particals from FGR or hypercholesterolemic pregnant. The embryonic development, zygote division, the oxidative and inflamitive state and genes expression related to lipid transported were measured. Finally, HDL from hypercholesterolemic or FGR pregnant women and 27-hydroxycholesterol were used to treat cultured trophoblast cells, effects on the cell division, differentiation, and lipid metabolism were studied.